Transcriptional control of blood cell emergence

Abstract

The haematopoietic system is established during embryonic life through a series of developmental steps that culminates with the generation of haematopoietic stem cells. Characterisation of the transcriptional network that regulates blood cell emergence has led to the identification of transcription factors essential for this process. Among the many factors wired within this complex regulatory network, ETV2, SCL and RUNX1 are the central components. All three factors are absolutely required for blood cell generation, each one controlling a precise step of specification from the mesoderm germ layer to fully functional blood progenitors. Insight into the transcriptional control of blood cell emergence has been used for devising protocols to generate blood cells de novo, either through reprogramming of somatic cells or through forward programming of pluripotent stem cells. Interestingly, the physiological process of blood cell generation and its laboratory‐engineered counterpart have very little in common.

Developmental trajectory of pre-hematopoietic stem cell formation from endothelium

“…Notably, neither the -371 nor +23 enhancers contain SOX motifs, which are recognized by a repressor of Runx1 expression, Sox17 . Other TF motifs enriched in the 27 called Runx1 enhancers, all of which are predicted to interact with P1, include ETS, FOX, SOX, KLF/SP, RUNX, and SMAD, which are recognized by TFs with well-documented roles in HSPC formation (Blank and Karlsson, 2011;Gilmour et al, 2019;Menegatti et al, 2019).…”

Haematopoietic stem cell reprogramming and the hope for a universal blood product

“…A separate review published in this issue of FEBS Letters is concerned with the provenance of haematopoietic cells during development, especially regarding the spatio-temporal expression patterns of key transcription factors [23]. A separate review published in this issue of FEBS Letters is concerned with the provenance of haematopoietic cells during development, especially regarding the spatio-temporal expression patterns of key transcription factors [23].…”

“…With all of these drawbacks in mind, and being aware that epigenetic memory is an issue, ECs themselves emerged as a potential starting point for HSC reprogramming. A separate review published in this issue of FEBS Letters is concerned with the provenance of haematopoietic cells during development, especially regarding the spatio-temporal expression patterns of key transcription factors [23]. Here, it suffices to say that the earliest measurable HSCs emerge from a specialized vascular tissue, haemogenic endothelium, located in the dorsal aspect of the aorta-gonad-mesonephros (AGM) region of the fish [24], amphibian [25], avian [26] and mammalian [27,28] mesoderm by a process termed endothelial-to-haematopoietic transition (EHT) [29].…”

Stem cell reprogramming: blood, neurons, and beyond

“…They discuss the most exciting recent developments in the field, focusing on hematopoietic [1][2][3][4][5] and neural [6][7][8][9][10] (stem) cell generation/reprogramming in vitro. In this Special Issue of FEBS Letters entitled 'Neural and Hematopoietic Stem Cell Reprogramming', we present a collection of peer-reviewed original articles and reviews authored by select international experts.…”

“…In short, Chen et al [1] discuss the recent progress in blood cell reprogramming and the potential use of these cells for disease modeling and therapeutic development; Dur an et al [2] compare and discuss the reprogramming methods used to generate hematopoietic stem and progenitor cells; Daniel et al [3] describe an improved human hemogenic induction protocol for establishing an in vitro model of human hematopoiesis, which may facilitate disease modeling and provide a basis for a platform for cell-based therapeutics; Hansen et al [4] discuss the derivation of erythroid, megakaryoid, and myeloid cells from iPSCs and the obstacles currently hindering therapeutic use; Menegatti et al [5] review the complex transcriptional network regulating blood cell generation during embryonic development and how this information can help in generating these cells in vitro; Traxler et al [6] report the most recent advances in direct induced neural (iN) conversion and compare this to other reprogramming-based neural cell models; Greiner et al [7] highlight the implications of sex-related intrinsic mechanisms and different adult stem cell populations (e.g., mesoderm-derived stem cells, neural stem cells, neural crest-derived stem cells) for stem cell differentiation and regeneration and for the design of new treatment options; Erharter et al [8] discuss different approaches to generate induced neural stem cells (iNSCs) and their promising use for disease modeling, autologous cell therapy, and personalized medicine; Birtele et al [9] report that adding neuronal-specific microRNAs into different culture media improves neuronal maturation and the acquisition of electrophysiological properties during direct neural reprogramming; and finally, Denoth-Lippuner and Jessberger [10] take a broader perspective discussing how reprogramming might lead to the rejuvenation of a cell, an organ, or even the whole organism.…”