Berrio Alejandro, Miranda Esther, Massri Abdull J, Afanassiev Anton, Schiebinger Geoffrey, Wray Gregory A, McClay David R
Department of Biology, Duke University, Durham, NC 27708, USA.
Department of Mathematics, University of British Columbia, 121-1984 Mathematics Road, Vancouver, BC V6T 1Z2, Canada.
Development. 2024 Dec 15;151(24). doi: 10.1242/dev.203152. Epub 2024 Dec 20.
Regulative development, demonstrated by many animal embryos, is the ability to replace missing cells or parts. The underlying molecular mechanism(s) of that ability is not well understood. If sea urchin micromeres (skeletogenic cell progenitors) are removed at the 16-cell stage, early endoderm initiates a sequential switch in cell fates, called transfating. Without micromeres, other mesoderm cells are absent as well, because their specification depends on signaling from micromeres. Most mesoderm cells later return by transfating, but pigment cells do not. Single-cell RNA sequencing, tracked over time, reveals the reprogramming sequence of those replacements. Beginning with an early endoderm specification state, cells progress through endomesoderm, then mesoderm, and finally distinct skeletogenic and blastocoelar cell specification states emerge, but pigment cells do not. Rescue of pigment cells was found to be a consequence of signal timing: if Delta is expressed prior to Nodal, pigment cells return. Thus, transfating operates through a series of gene regulatory state transitions, and reprogramming fails if endogenous negative signals occur prior to positive signals in the reprogramming sequence.
许多动物胚胎所表现出的调节性发育，是指替换缺失细胞或部分的能力。这种能力背后的分子机制尚未得到充分理解。如果在16细胞阶段去除海胆小分裂球（骨骼生成细胞祖细胞），早期内胚层会启动细胞命运的顺序转换，称为转分化。没有小分裂球，其他中胚层细胞也不存在，因为它们的特化依赖于来自小分裂球的信号。大多数中胚层细胞后来通过转分化恢复，但色素细胞不能。随着时间推移进行的单细胞RNA测序揭示了这些替代细胞的重编程序列。从早期内胚层特化状态开始，细胞依次经过内中胚层、然后是中胚层，最终出现不同的骨骼生成细胞和囊胚腔细胞特化状态，但色素细胞不能。研究发现色素细胞的恢复是信号时间的结果：如果Delta在Nodal之前表达，色素细胞就会恢复。因此，转分化通过一系列基因调控状态转变起作用，如果在重编程序列中内源性负信号先于正信号出现，重编程就会失败。
