Interkingdom Comparison of Threonine Metabolism for Stem Cell Maintenance in Plants and Animals

Abstract

In multicellular organisms, tissue generation, maintenance, and homeostasis depend on stem cells. Cellular metabolic status is an essential component of different differentiated states, from stem to fully differentiated cells. Threonine (Thr) metabolism has emerged as a critical factor required to maintain pluripotent/multipotent stem cells in both plants and animals. Thus, both kingdoms conserved or converged upon this fundamental feature of stem cell function. Here, we examine similarities and differences in Thr metabolism-dependent mechanisms supporting stem cell maintenance in these two kingdoms. We then consider common features of Thr metabolism in stem cell maintenance and predict and speculate that some knowledge about Thr metabolism and its role in stem cell function in one kingdom may apply to the other. Finally, we outline future research directions to explore these hypotheses.

L-threonine mediated DAF-16/HSF-1 activation inhibits ferroptosis and increases healthspan

“…These observations and manifestations associated with ferritin homeostasis and its turnover are crucial factors to human health and organismal energy balance 54 . So far most of the positive effects of threonine are linked to enhanced immunity, through mucus formation 18,42 , and stimulation of pluripotency of embryonic stem cells [12][13][14][15] . Here, we propose another angle how threonine can achieve health-and lifespan benefits in C. elegans through the attenuation of cellular ferroptosis.…”

“…In the case of L-threonine, it was reported that threonine metabolism was a crucial factor for stem cell maintenance and renewal by influencing histone methylation [12][13][14][15] . Moreover, as a major component of mucins, threonine plays a conclusive role in the maintenance of mucosal integrity, barrier constitution, and eventually immune function regulation [16][17][18][19] .…”

Amino Acid Transport and Metabolism Regulate Early Embryo Development: Species Differences, Clinical Significance, and Evolutionary Implications

“…Likewise, Thr transport and metabolism support stem cell maintenance in both animals and plants, so this reliance on Thr may be an ancient mechanism to conserve stem cell proliferation in multicellular organisms [12]. Similarly, Glu production from Lys seems to support the maintenance of pluripotency in ICM cells of mammalian blastocysts [24], while, in plants, this Glu production regulates their environmental responses and growth [103].…”

“…Thr transporters in eukaryotic stem cells may function as transceptors to help maintain their proliferation [1,12]. Similarly, in most animals, TDH-regulated Thr metabolism, to form Gly and subsequently H3K4me3, likely maintains their pluripotent ES progenitor cells in the ICM [1,12]. In TDH-deficient hES progenitor cells, Gly and H3K4me3 are likely formed from Ser synthesized in the cells [64].…”

“…In the inner cell masses (ICMs) of mammalian blastocysts, and probably the stem cells of other multicellular species including plants, amino acid transport and metabolism support and regulate the maintenance of pluripotency [12]. For example, threonine transport and metabolism in the embryonic stem (ES) of mice and their progenitor (ICM) cells selectively foster the trimethylation of lysine residue 4 in histone H3 (i.e., H3K4me3 formation).…”